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Nobuo Fukuda

Publications and source records attributed to Nobuo Fukuda.

At least 19 recordsLinked to original sources
PubMed2006

Dose-response relationship for life-shortening and carcinogenesis in mice irradiated at day 7 postnatal age with dose range below 1 Gy of gamma rays.

This study was designed to elucidate the dose-response relationships for life-shortening and tumorigenic effect in the dose range below 1 Gy of gamma rays delivered during the infant period. Female B6C3F1 mice were irradiated with 0.10, 0.48 or 0.95 Gy at 7 days of age. All irradiated mice were allowed to live out their entire life span together with a simultaneously ongoing control group under a specific pathogen-free condition. Shortening of the mean life span was 1.58% in mice irradiated with 0.10 Gy, which was statistically significant . The coefficient of the linear dose-response relationship for life-shortening was 11.21% Gy(-1). The attributable death fraction for all causes of death in 0.10 Gy group reached 0.092. The excess relative risk for death rate from all causes was 0.102 in the group irradiated with 0.10 Gy. The coefficient of the linear dose-response relationship of the excess relative risk for death rate from all causes was 1.30 Gy(-1). The mean number of types of solid tumors at the time of death in mice irradiated with 0.10 Gy was distinctly larger than that in the control group. The excess relative risk for death rate from solid tumors was 0.45 in mice irradiated with 0.10 Gy. The coefficient of the linear dose-response relationship of excess relative risk for death rate from solid tumors was 4.52 Gy(-1). Increase in incidences of the pituitary, ovarian and adrenal tumors was observed in mice irradiated with 0.10 Gy. The results of the present study showed that infant mice are susceptible to solid tumor induction, especially of the endocrine organs.

Aging↗
PubMed2005

Temporal variation of excess mortality rate from solid tumors in mice irradiated at various ages with gamma rays.

The influence of age at the time of irradiation on the lifetime risk for excess mortality from solid tumors, and on the temporal pattern of variation in the excess mortality rate, was analyzed using data obtained from a study of female B6C3F1 mice, which was conducted at the National Institute of Radiological Sciences, Chiba, Japan. Mice were irradiated with 1.9-Gy gamma rays at day 17 in intra-uterine age, or day 0, 7, 35, 105 or 365 in postnatal age. Control and irradiated mice were allowed to live out their entire life span under a specific pathogen-free condition. The primary cause of death for each mouse was determined by macroscopic and microscopic examination. The lifetime excess mortality from solid tumors was apparently higher in the mice irradiated during the neonatal to puberty period than in the mice irradiated during the intra-uterine or adult period. The median of time for manifestation of lifetime excess mortality since irradiation was shortest among mice exposed at 365 days of age and longest among mice exposed at 17 days of intra-uterine age. The excess mortality rate at any attained age was not independent of the age at irradiation. The excess mortality rate increased with increasing age, and the excess relative risk decreased with increasing age. The temporal variations of the excess mortality rate and background mortality rate were analyzed using the additive multi-stage model, which includes the assumptions that radiation-related carcinogenesis superimposes on background carcinogenesis, and that both radiation-related and background carcinogenesis involve multiple stages. The results of the analysis strongly suggested that the number of stages for manifestation of radiation-related carcinogenesis was less than that in background carcinogenesis for various types of solid tumors, and that the majority of stages were common in both radiation-related and background carcinogenesis. The additive multi-stage model well described the observed findings on the length of the latent period and temporal variations of the excess mortality rate and excess relative risk. It should be stressed that the magnitude of the lifetime risk was not only determined by a decrease in the number of hits for carcinogenesis but was also determined by another parameter which decides the initial value of excess mortality rate. Furthermore, we estimated the rate of decrease in the number of remaining hits for carcinogenesis, and it was found that the rate of decrease in the number of remaining hits was higher in several irradiated groups than that in the background carcinogenesis. However, radiation-induced genomic instability and/or delayed mutation may be of secondary importance when radiation was delivered promptly, because the present analysis revealed that the major action of radiation took place soon after irradiation, as one or more hits for transitions of stages for carcinogenesis.

Age Factors↗
PubMed2004

Lipid-altering changes and pleiotropic effects of atorvastatin in patients with hypercholesterolemia.

In this prospective study, we found beneficial short-term effects from atorvastatin therapy, including effects on low-density lipoprotein subfractions and remnant-like lipoprotein particle cholesterol, antioxidant effects, and alterations in endothelial function that may be important in early benefit from statin therapy; some effects would support much earlier benefit than previously reported. We also found long-term effects of atorvastatin, including decreased plasminogen activator inhibitor type-1 and additional significant alterations in low-density lipoprotein subfractions and endothelial function, supporting benefits from continuous long-term atorvastatin therapy beyond early reversal of hypercholesterolemia.

Adult↗
PubMed2004

Diagnosis of cardiac amyloidosis based on the myocardial velocity profile in the hypertrophied left ventricular wall.

The myocardial velocity profile (MVP), derived from color-coded tissue Doppler imaging (TDI), can identify transmural heterogeneity based on the physiology and pathology of the myocardium. This study sought to clarify whether the MVP can differentiate cardiac amyloidosis from other causes of left ventricular hypertrophy. We recorded the MVP and determined its myocardial velocity gradient (MVG) in the ventricular septum and left ventricular posterior wall using color-coded TDI in 10 patients with cardiac amyloidosis, in 25 patients with hypertensive hypertrophied left ventricular wall, in 25 patients with asymmetric septal hypertrophy of hypertrophic cardiomyopathy, and in 20 clinically normal controls. End-diastolic ventricular septal thickness was similar among the cardiac amyloidosis, hypertension, and hypertrophic cardiomyopathy groups. Percent systolic thickening of the ventricular septum and left ventricular posterior wall calculated from M-mode left ventricular echocardiograms was lower in the cardiac amyloidosis group than in the hypertension, hypertrophic cardiomyopathy, or control group. Peak MVGs during systole and early diastole were lowest in the cardiac amyloidosis group, followed, in order, by the control, hypertension, and hypertrophic cardiomyopathy groups. The systolic and early diastolic MVPs in the ventricular septum and left ventricular posterior wall showed a characteristic serrated pattern in all patients with cardiac amyloidosis, but not in any other patient groups. In conclusion, MVPs in the ventricular septum and left ventricular posterior wall show a distinctive serrated pattern that may be related to amyloid deposition in the myocardium. Myocardial tissue characterization using color-coded TDI provides diagnostic information in patients with cardiac amyloidosis.

Adult↗
PubMed2004

Atrial electrophysiologic abnormalities in patients with Wolff-Parkinson-White syndrome but without paroxysmal atrial fibrillation.

BACKGROUND: Paroxysmal atrial fibrillation (PAF) frequently occurs in patients with Wolff-Parkinson-White (WPW) syndrome. HYPOTHESIS: The purpose of this study was to analyze the atrial electrophysiologic abnormalities and vulnerability to develop atrial fibrillation (AF) in patients with WPW syndrome but with no previous history of PAF. METHODS: We investigated atrial electrophysiologic abnormalities and vulnerability to AF in patients with WPW syndrome but without PAF. An electrophysiologic study was performed in 28 patients with WPW syndrome, 23 with atrioventricular nodal reentrant tachycardia (AVNRT) and 25 with other arrhythmias (control), all of whom had no history of PAF. The following atrial excitability parameters were assessed: effective refractory period (ERP), spontaneous or paced (A1) and extrastimulated (A2) atrial electrogram widths, percent maximum atrial fragmentation (%MAF; A2/A1 x 100), wavelength index (WLI; ERP/A2), and inducibility of AF. RESULTS: The ERP tended to be shorter in patients with WPW syndrome and in those with AVNRT than in the control group. The %MAF increased (154 +/- 33 vs. 137 +/- 23%, p < 0.05) and WLI decreased (2.7 +/- 0.8 vs. 3.4 +/- 1.0, p < 0.05) significantly in patients with WPW syndrome compared with the control group; however, these parameters in patients with AVNRT showed intermediate values. Atrial fibrillation was more inducible in patients with WPW syndrome (4/28 [14.3%]) than in those with AVNRT (4.3% [1/23]) and the control group (0/25 [0%]). With respect to patients with WPW syndrome and with and without inducible AF, the %MAF increased (195 +/- 23 vs. 148 +/- 30%, p < 0.01) and the WLI decreased (2.2 +/- 0.3 vs. 2.9 +/- 0.9, p < 0.05) in subjects with inducible AF. CONCLUSIONS: Atrial electrophysiologic abnormalities, especially atrial conduction delays, are more prominent in patients with WPW syndrome, even if they had no previous history of PAF. These abnormalities may play an important role in determining the vulnerability to AF.

Adolescent↗
PubMed2004

Time course differences for statin-induced pleiotropic effects in hypercholesterolemic patients.

BACKGROUND: It is unclear whether there are temporal differences for the pleiotropic effects for different members of the statin class. The present study investigated differences in the short- and intermediate-term pleiotropic effects of statins in hypercholesterolemic patients. METHODS: Thirty-five hypercholesterolemic patients were randomly treated with either atorvastatin or cerivastatin for 3 months. We measured fasting lipid concentrations, thiobarbituric acid reactive substances (TBARS), fibrinolytic parameters, and flow-mediated dilation of the brachial artery (FMD) at baseline and after 2 weeks and 3 months of therapy. RESULTS: After 2 weeks of therapy, atorvastatin decreased the low density lipoprotein (LDL) cholesterol, small, dense LDL cholesterol (34+/-22 vs. 18+/-20%, P<0.01), remnant-like particles (RLP) cholesterol (8.8+/-6.0 vs. 5.1+/-2.6 mg/ml, P<0.01), and TBARS (3.3+/-1.0 vs. 3.1+/-0.9 nmol/ml, P<0.05), and cerivastatin decreased LDL cholesterol. After 3 months of therapy, atorvastatin decreased small dense LDL cholesterol (8+/-13%, P<0.0001) additionally, and cerivastatin decreased small, dense LDL cholesterol (51+/-11 vs. 12+/-22%, P<0.0001) and plasminogen activator inhibitor type 1 (68+/-32 vs. 51+/-21 ng/ml, P<0.05). FMD increased significantly in both groups after 2 weeks, although the relative change in FMD was greater with cerivastatin therapy after 2 weeks than atorvastatin therapy (60+/-78 vs. 23+/-26%, P<0.05). However, FMD was the same for both groups after 3 months (58+/-65 vs. 66+/-61%, NS), because atorvastatin additionally increased FMD. There was no correlation between these pleiotropic effects and the improvement in the lipid profile for either group. CONCLUSIONS: These findings suggest that the degree of pleiotropic effect as well as the time course for the effect are different among members of the statin class of drugs.

Adult↗
PubMed2004

Elevated concentration of soluble vascular endothelial cadherin is associated with coronary atherosclerosis.

BACKGROUND: Vascular endothelial (VE)-cadherin, a Ca(2+)-dependent cell adhesion molecule, is expressed in atherosclerotic lesions by endothelial cells and is associated with neovascularization, although the relationship between circulating VE-cadherin and coronary artery disease has not been studied. METHODS AND RESULTS: The plasma concentration of VE-cadherin was measured in peripheral blood (femoral artery) and the coronary sinus of 24 patients with acute myocardial infarction (AMI), 26 with stable angina pectoris (AP), 18 with old myocardial infarction (OMI), and 30 control subjects (Control) who had no coronary artery stenosis on angiography. For the patients with AMI, blood samples were obtained in the acute (day 1) and chronic (day 21) phases. The plasma concentration of VE-cadherin was measured by enzyme-linked immunosorbent assay. The correlation between the plasma VE-cadherin concentration and the Gensini score was also determined as an index of the severity of coronary atherosclerosis. The plasma concentrations of VE-cadherin (ng/ml) in both the peripheral and coronary sinus blood were higher in patients with AMI, AP, and OMI than in the control subjects, and were similar in the 3 groups with coronary artery disease (femoral artery: AMI 5.1+/-2.5, AP 4.7+/-2.4, OMI 4.5+/-3.3, Control 2.6+/-2.3; coronary sinus: AMI 5.6+/-2.6, AP 5.0+/-2.3, OMI 5.0+/-2.9, Control 2.4+/-2.1, respectively). Plasma VE-cadherin concentrations were higher in the coronary sinus than peripheral blood samples in patients with AMI (p<0.01), AP (p<0.01), and OMI (p<0.05). The plasma VE-cadherin concentration was the same in the acute and chronic phases in patients with AMI. In the 3 groups of patients with coronary disease, both the peripheral plasma VE-cadherin concentration and the coronary sinus concentration correlated with the Gensini score (r=0.32, p<0.01 and r=0.42, p<0.001, respectively). Multiple regression analysis revealed that the plasma VE-cadherin concentration predicted the Gensini score independently of sex, age, hypertension, diabetes mellitus, smoking, and the lipid profiles. CONCLUSION: Increased secretion of VE-cadherin from the epicardial arteries is associated with the degree of coronary atherosclerosis, indicating the presence of atherosclerosis rather than disease activity.

Aged↗
PubMed2003

Increased soluble platelet/endothelial cell adhesion molecule-1 in the early stages of acute coronary syndromes.

Specific molecules including inflammatory cell adhesion molecules mediate attachment of blood leukocyte and platelets to the endothelium and mononuclear cell migration into the arterial intima. However, the clinical significance of soluble cell adhesion molecules very early in the course of acute coronary syndrome is not known. We assayed platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31), intercellular adhesion molecule-1 (ICAM-1, CD54), and P-selectin (CD62P) in plasma obtained from 20 patients within 3 h after the onset of acute myocardial infarction (AMI); 16 patients with unstable angina pectoris; 20 patients with stable angina pectoris, and 28 controls. Blood samples were obtained on hospital admission and again 1 week after onset of AMI and unstable angina, and on admission in patients with stable angina and controls. Plasma PECAM-1 concentration (ng/ml) on admission was higher in patients with AMI (25.6+/-4.7) and unstable angina (24.7+/-4.4) than in stable angina (20.5+/-4.4) and control (18.8+/-3.8) groups. In both AMI and unstable angina, plasma PECAM-1 had decreased significantly by 1 week (AMI, 20.8+/-4.0; unstable angina, 21.0+/-4.1). Plasma ICAM-1 concentration (ng/ml) on admission was higher in patients with AMI (254+/-70), unstable angina (264+/-78), and stable angina (245+/-68) than in controls (201+/-56), but did not differ between the three coronary syndromes. Plasma P-selectin concentration did not differ between the four groups, including controls. Therefore, soluble PECAM-1 concentration may be a sensitive markers providing early diagnostic aid in acute coronary syndromes.

Aged↗
PubMed2003

Relation of age and sex to atrial electrophysiological properties in patients with no history of atrial fibrillation.

Although atrial fibrillation is a common arrhythmia, especially in elderly men, little is known about age related changes in atrial electrophysiological properties or gender differences. The aim of this study was to analyze the effects of aging on vulnerability to atrial fibrillation and assessed gender differences in those age related changes. An electrophysiological study was performed on 73 patients with no history of atrial fibrillation, structural heart disease, or conditions with potential effects on cardiac hemodynamic or electrophysiological function, including 25 women (mean age 49 +/- 18 years; range 12-84 years). The following atrial excitability parameters were assessed: spontaneous or paced (A1) and extrastimulated (A2) atrial electrogram widths, percent maximum atrial fragmentation (A2/A1 x 100), effective refractory period, wavelength index (effective refractory period/A2), and inducibility of atrial fibrillation. There were no significant differences in percent maximum atrial fragmentation (143 +/- 28 vs 142 +/- 35%), effective refractory period (241 +/- 39 vs 238 +/- 50 ms), wavelength index (2.9 +/- 0.8 vs 3.1 +/- 0.9), induction of atrial fibrillation (10 [21%] vs 7 [28%]), or age (50 +/- 17 vs 49 +/- 20 years) between men and women. Age was not statistically different between those patients with and without induction of atrial fibrillation in men (48 +/- 14 vs 50 +/- 18 years) and women (48 +/- 18 vs 49 +/- 21 years). Percent maximum atrial fragmentation and effective refractory period were directly correlated with age in men (r = 0.35, P = 0.01; r = 0.46, P < 0.001, respectively) and women (r = 0.42, P = 0.04; r = 0.45, P = 0.02, respectively), though wavelength index did not correlate with age in men (r = -0.04) or women (r = -0.04) with no history of atrial fibrillation. Considering these findings, the authors conclude that the mechanism triggering atrial fibrillation may be different between older and younger patients with atrial fibrillation, because younger patients who have no marked substrate for atrial fibrillation may need many trigger beats to induce atrial fibrillation.

Adolescent↗
PubMed2003

Effects of atorvastatin therapy on the low-density lipoprotein subfraction, remnant-like particles cholesterol, and oxidized low-density lipoprotein within 2 weeks in hypercholesterolemic patients.

The short- and intermediate-term pleiotropic effects of atorvastatin were investigated in 18 hypercholesterolemic patients, as well as the temporal differences in these pleiotropic effects. Atorvastatin was given for 3 months and fasting lipid concentrations, thiobarbituric acid reactive substances (TBARS), fibrinolytic parameters, and flow-mediated dilation of the brachial artery (FMD) were measured at baseline and after 2 weeks and 3 months of therapy. Atorvastatin reduced the total cholesterol (273+/-34 vs 188+/-31 mg/dl, p<0.0001), low-density lipoprotein-cholesterol (LDL-C: 174+/-28 vs 111+/-23 mg/dl, p<0.0001), small, dense LDL-C (34+/-22 vs 18+/-20%, p<0.01), remnant-like particles cholesterol (RLP-C: 8.8+/-6.0 vs 5.1+/-2.6 mg/ml, p<0.01), and TBARS (3.3+/-1.0 vs 3.1+/-0.9 nmol/ml, p<0.05) after 2 weeks. Atorvastatin decreased the concentration of small, dense LDL-C again after 3 months (8+/-13%, p<0.0001). The plasma concentrations of the fibrinolytic parameters did not change significantly after 3 months of atorvastatin therapy. FMD increased significantly after 2 weeks (5.6+/-2.1 vs 6.3+/-2.0%, p<0.01) and additionally increased after 3 months of therapy (8.3+/-1.9%, p<0.0001). There were no correlations between the pleiotropic effects and the improvement in the lipid profile. The results indicate some short-term pleiotropic effects of atorvastatin therapy within 2 weeks, which may be important with respect to the early benefits of statin therapy.

Aged↗
PubMed2003

Age-related changes in the electrophysiologic properties of the atrium in patients with no history of atrial fibrillation.

Although atrial fibrillation is a common arrhythmia, especially in the elderly, little is known about age-related changes in the electrophysiologic properties of the atrium. The aim of this study was to analyze the effect of aging on atrial vulnerability to atrial fibrillation. An electrophysiologic study was performed in 45 patients with no history of atrial fibrillation, Wolff-Parkinson-White syndrome, structural heart disease, or conditions with potential effects on cardiac hemodynamic or electrophysiologic function (15 females; mean age, 52 +/- 18 years; range, 14 to 84 years). The following atrial excitability parameters were assessed: spontaneous or paced (A1) and extrastimulated (A2) atrial electrogram widths, percent maximum atrial fragmentation (A2/A1 x 100), effective refractory period, wavelength index (ERP/A2), and inducibility of atrial fibrillation. Atrial fibrillation was induced in 9 patients. Percent maximum atrial fragmentation was greater (176 +/- 36 vs 137 +/- 26%, P < 0.001) and wavelength index was shorter (2.4 +/- 0.4 vs 3.2 +/- 0.9, P < 0.01) in the patients with than without inducible atrial fibrillation. However, age was similar in patients with and without inducible atrial fibrillation (47 +/- 11 vs 53 +/- 19 years, P = 0.36). Percent maximum atrial fragmentation and effective refractory period directly correlated with age (r = 0.32, P < 0.05 and r = 0.45, P < 0.001, respectively). On the other hand, wavelength index (3.1 +/- 0.9) did not correlate with age (r = -0.05, P = 0.77). This study suggests that the mechanism triggering atrial fibrillation may be very well different between older and younger patients with atrial fibrillation, because younger patients have no marked substrate for atrial fibrillation.

Adolescent↗
PubMed2003

Plasma levels of brain natriuretic peptide in various forms of obstruction to the left ventricular outflow tract.

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the relationship between plasma concentrations of brain natriuretic peptide (BNP) and the type or degree of stenosis in the left ventricular outflow tract (LVOT). METHODS: The relationship between BNP plasma level and pressure gradient (PG) in the LVOT and LV wall thickness (LVWth) was analyzed in 25 patients with a PG > or = 30 mmHg in the LVOT from the mid-left ventricle to the aortic valve. Among patients, 14 had aortic valve stenosis (AS), five had subaortic type hypertrophic obstructive cardiomyopathy (HOCM), three had mid-ventricular type HOCM, and three had angled ventricular septum. Three patients with AS showed LV systolic dysfunction (ejection fraction (EF) < 50%). All patients were in sinus rhythm. LV peak-systolic pressure (LVPSP) was derived by adding maximum PG to cuff systolic arterial pressure. RESULTS: In AS patients without LV systolic dysfunction and HOCM patients, there was a significant positive correlation between BNP and LVPSP (r = 0.78, p = 0.001; r = 0.76, p = 0.007, respectively). In AS patients without LV systolic dysfunction, BNP was positively correlated with LVWth (r = 0.79, p = 0.001), but no correlation was found between BNP and LVWth in patients with HOCM. In AS patients including systolic LV dysfunction, BNP was negatively correlated with LVEF (r = -0.87, p < 0.0001), but no correlation was found between BNP and LVEF in patients with HOCM. CONCLUSION: These results suggest that BNP level is closely associated with severity of stenosis in patients with HOCM, but mainly with severity of stenosis and also degree of LV systolic dysfunction in patients with AS. The BNP-LVWth relationship appeared to differ between AS (a fixed stenosis with uniform myocardial hypertrophy) and HOCM (a dynamic stenosis with uneven myocardial hypertrophy).

Aged↗
PubMed2002

Effects of angiotensin II receptor antagonists on [(123)I]metaiodobenzylguanidine myocardial imaging findings and neurohumoral factors in chronic heart failure.

Previous studies have not investigated the ef-ficacy of angiotensin II (AII) receptor antagonists against cardiac sympathetic overactivity in patients with chronic heart failure (CHF) using [(123)I]metaiodobenzylguanidine (MIBG) myocardial imaging. We studied 34 CHF patients with fractional shortening of the left ventricular (LV) diameter <==25% or LV ejection fraction <==45% in echocardiograms. An AII receptor antagonist (losartan or candesartan) was administered. Before and 6 months after the administration, MIBG myocardial imaging and echocardiography were performed, and neurohumoral factors were investigated. MIBG imaging revealed that the antagonist did not significantly change the heart-to-mediastinum ratio. However, the washout rate fell significantly (from 32.6% +/- 7.6% to 28.2% +/- 7.5%; P < 0.001). No significant changes occurred in LV diameter, fractional shortening, or LV ejection fraction. Circulating atrial (ANP) and brain natriuretic peptides (BNP), and aldosterone fell significantly. Changes in the MIBG washout rate correlated positively with changes in BNP ( r = 0.35, P < 0.05). In 19 patients also being treated with angiotensin-converting enzyme (ACE) inhibitors, the MIBG washout rate also fell significantly with AII antagonists, as did BNP and aldosterone. The decreased MIBG washout and BNP in patients with CHF induced by the AII receptor antagonists suggests the efficacy of these agents in modifying cardiac sympathetic function and neurohumoral factors, even with ACE inhibition. Combination therapy with AII receptor antagonists and ACE inhibitors appears effective for CHF.

3-Iodobenzylguanidine↗
PubMed2002

Plasma concentrations of fibrinolytic factors in the subacute phase of myocardial infarction predict recurrent myocardial infarction or sudden cardiac death.

BACKGROUND: The prognostic value of plasma concentrations of tissue type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein has been reported in patients with coronary artery disease. However, the association between cardiac events and these factors during the acute and subacute phases of myocardial infarction (MI) is unknown. The purpose of this study was to determine whether elevated plasma concentrations of t-PA, PAI-1, and C-reactive protein in patients with MI are associated with future recurrent MI or sudden cardiac death. METHODS: We studied 106 consecutive patients who survived a confirmed first MI between 1993 and 1998 in our hospital. The control group consisted of 50 patients who had no significant coronary artery stenosis. Blood samples were obtained at the time of admission for acute MI and on the 28th day after admission. Patients were followed for a mean of 50 months after these measurements. The primary end points were sudden cardiac death and fatal or nonfatal acute MI. RESULTS: Of the 92 patients who were available for follow-up, 10 had cardiac events. Both the plasma t-PA and PAI-1 concentrations were elevated on day 1 of acute MI compared to the control group and decreased by day 28, but remained higher than those in the controls. Plasma C-reactive protein concentration was also elevated on day 1 and decreased by day 28. Using a stepwise variable choice model of Cox proportional hazards analysis including these fibrinolytic factors and C-reactive protein, only the t-PA concentration in the subacute phase was a significant predictor of cardiac events (relative risk per S.D. 3.20, P<0.01). We further found that independent of other risk factors, an elevated t-PA concentration was predictive of cardiac events. CONCLUSIONS: This study reveals that a rise in endogenous t-PA concentration during the subacute phase of MI could predict recurrent MI or sudden cardiac death.

Aged↗
PubMed2002

Serum hepatocyte growth factor predicts ventricular remodeling following myocardial infarction.

Hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) stimulate endothelial cell proliferation and induce angiogenesis, but the timing and significance of their release in patients with acute myocardial infarction (AMI) are unknown in relation to future left ventricular remodeling. Venous blood samples were obtained at admission and up to 3 weeks later in 40 patients with AMI and in 40 age- and sex-matched control subjects. Blood samples were also taken from the coronary sinus (CS) in 20 patients on day 7 following AMI. Left ventricular end-diastolic volume in the subacute (1 week) and chronic (3 months) phases was assessed by left ventriculography to identify the remodeling group (n=15), which was defined as an increase in left ventricular end-diastolic volume index > or =5 ml/m(2) relative to the baseline value. Serum HGF and VEGF concentrations were higher in newly admitted patients with AMI than in the controls (HGF, 0.33 +/-0.09 vs 0.24+/-0.08 ng/ml, p<0.01; VEGF, 92.2+/-43.1 vs 67.2+/-29.8 pg/ml, p<0.01), peaking on day 7 (HGF, 0.41+/-0.12; VEGF, 161.7+/-76.9), and gradually decreasing between days 14 and 21. The HGF concentration in the CS did not differ from the concentration in the periphery, but the VEGF concentration was significantly more abundant in the CS than in the peripheral sample on day 7 (p<0.05). The serum HGF concentration on day 7 was higher in the remodeling group than in the nonremodeling group (0.47 +/-0.13 vs 0.36+/-0.09 ng/ml, p<0.01), but there was no difference between the groups on admission, day 14 and day 21. The serum VEGF concentration did not differ between the remodeling and nonremodeling groups at any time. Thus, the serum HGF concentration on day 7 after AMI is mostly from noncardiac sources and predicts left ventricular remodeling.

Aged↗
PubMed2002

Dose-response relationship for lifetime excess mortality and temporal pattern of manifestation in mice irradiated neonatally with gamma rays.

The dose-response relationships for the lifetime excess mortality and temporal distribution of excess mortality were analysed using a data set from an experiment on the long-term effects of gamma irradiation in neonatal mice. The excess mortality was calculated based on an assumption that any increase in the mortality rate was attributable to radiation exposure. The dose-response relationship for the lifetime excess mortality was convex upward, whereas the shortening of the mean life span was proportional to the dose. The excess mortality at 1 Gy was estimated to be 35.6%. The relative risk decreased markedly with increasing age. However, the mortality rate in the irradiated group was persistently higher than the background rate of death, and the absolute risk increased with age. A logistic specification was used to analyze the temporal distribution of the excess mortality. The results of the analysis indicated a dose-dependent shortening of the latent period and a broadening of the distribution.

Aging↗